Diffusion of gases across the alveolar-capillary barrier is traditionally measured with carbon monoxide (CO), which is then used to calculate diffusion rates for other gases. Preliminary studies indicate that several gases (CO, CO2, He, SF6, HCN and methane thiol) do not diffuse at rates predicted by the traditional calculations based on solubilities (water or oil) and molecular weights. We plan to measure diffusion of several gases across the alveolar-capillary barrier and compare results of various gases with one another and with predicted rates. This will improve basic understanding of gas diffusion through lung tissue and determine validity of calculating diffusion of other gases on the basis of CO diffusion. Two different experimental preparations will be used: (1) perfusion of isolated dog lung lobes with a solution able to rapidly absorb the chosen gases. Gases, concentrations, and solutions are chosen to produce at least partial diffusion limitation as the gases cross the alveolar-capillary barrier. Diffusing capacity for each is measured using the rebreathing technique of Adaro et al. (1973), sampling the gas in the rebreathing circuit with a Balzer quadrupole mass spectrometer; (2) diffusion across compressed sections of lung tissue mounted in a plexiglass chamber. Although less physiological than the perfused lobe studies, these measurements have the advantages that more gases can be studied because any gas is diffusion limited in this situation, we are not limited to gases which can be bound in the perfusate, and the results can be compared with measurements across simple layers of water, lipid, or other liquids of interest. Solubilities of each of the gases used will be measured in water, lipid, and tissue homogenate so that diffusion rates can be compared to rates predicted from solubility. We plan to use gases of widely differing solubilities in water and lipid (SF6 and methane thiol, for example), differing molecular weights (He and SF6, for example) and differing degrees of ionization in water (He vbs. CO2, for example).